2023
Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Tarantino P, Gupta H, Hughes M, Files J, Strauss S, Kirkner G, Feeney A, Li Y, Garrido-Castro A, Barroso-Sousa R, Bychkovsky B, DiLascio S, Sholl L, MacConaill L, Lindeman N, Johnson B, Meyerson M, Jeselsohn R, Qiu X, Li R, Long H, Winer E, Dillon D, Curigliano G, Cherniack A, Tolaney S, Lin N. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer. Nature Communications 2023, 14: 7496. PMID: 37980405, PMCID: PMC10657399, DOI: 10.1038/s41467-023-43324-w.Peer-Reviewed Original ResearchConceptsHER2-low tumorsBreast cancerHER2-negative metastatic breast cancerMetastatic breast cancerTumor mutational burdenHigh rateComprehensive genomic characterizationHER2 0Mutational burdenBreast tumorsTumorsHER2Genomic alterationsNext-generation sequencingSignificant differencesGenomic findingsCancerGenomic landscapeMolecular underpinningsHemideletionGenomic characterizationHigher numberPatientsCopy counts
2022
STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
Wang Q, Bergholz JS, Ding L, Lin Z, Kabraji SK, Hughes ME, He X, Xie S, Jiang T, Wang W, Zoeller JJ, Kim HJ, Roberts TM, Konstantinopoulos PA, Matulonis UA, Dillon DA, Winer EP, Lin NU, Zhao JJ. STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer. Nature Communications 2022, 13: 3022. PMID: 35641483, PMCID: PMC9156717, DOI: 10.1038/s41467-022-30568-1.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityBreast cancerPARP inhibitorsSTING agonistsBRCA-mutant breast cancerTumor cellsAnti-tumor stateAdvanced ovarian tumorsCell-mediated suppressionType I IFN responseTumor-associated macrophagesInnate immune suppressionI IFN responseBreast tumor cellsTreatment landscapePro-tumor macrophagesImmune suppressionOvarian tumorsImmune cellsBRCA mutationsSystemic administrationT cellsMouse modelTherapeutic benefitBreast tumors
2019
Impact of a Pre-Operative Exercise Intervention on Breast Cancer Proliferation and Gene Expression: Results from the Pre-Operative Health and Body (PreHAB) Study
Ligibel JA, Dillon D, Giobbie-Hurder A, McTiernan A, Frank E, Cornwell M, Pun M, Campbell N, Dowling RJO, Chang MC, Tolaney S, Chagpar AB, Yung RL, Freedman RA, Dominici LS, Golshan M, Rhei E, Taneja K, Huang Y, Brown M, Winer EP, Jeselsohn R, Irwin ML. Impact of a Pre-Operative Exercise Intervention on Breast Cancer Proliferation and Gene Expression: Results from the Pre-Operative Health and Body (PreHAB) Study. Clinical Cancer Research 2019, 25: 5398-5406. PMID: 31018921, DOI: 10.1158/1078-0432.ccr-18-3143.Peer-Reviewed Original ResearchConceptsPre-operative healthBreast cancerExercise interventionKi-67Exercise participantsLower cancer-specific mortalityPre-operative exercise interventionCancer-specific mortalityControl participantsBody mass indexTumor immune infiltratesImpact of exerciseBreast cancer proliferationMinutes/weekBreast cancer diagnosisOpportunity trialBaseline biopsiesImmune infiltratesMass indexSurgical excisionMean ageIntervention periodGene expressionChanges of expressionBreast tumorsThe Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy
Waks AG, Stover DG, Guerriero JL, Dillon D, Barry WT, Gjini E, Hartl C, Lo W, Savoie J, Brock J, Wesolowski R, Li Z, Damicis A, Philips AV, Wu Y, Yang F, Sullivan A, Danaher P, Brauer HA, Osmani W, Lipschitz M, Hoadley KA, Goldberg M, Perou CM, Rodig S, Winer EP, Krop IE, Mittendorf EA, Tolaney SM. The Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy. Clinical Cancer Research 2019, 25: 4644-4655. PMID: 31061067, PMCID: PMC6677598, DOI: 10.1158/1078-0432.ccr-19-0173.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesImmune microenvironmentNeoadjuvant chemotherapyPD-L1Breast cancerHormone receptor-positive breast cancerBreast tumorsHormone receptor-positive/HER2-negative breast cancerHER2-negative breast cancerDistant metastasis-free survivalReceptor-positive breast cancerImmunotherapy-based approachesPAM50 intrinsic subtypesCheckpoint inhibitor therapyPD-L1 stainingTumor-infiltrating lymphocytesMetastasis-free survivalMacrophage-targeted therapiesRole of macrophagesPreoperative chemotherapyStandard chemotherapyInhibitor therapyResidual diseaseMyeloid signaturePoor responseCharacterization of mutational processes in ER+ metastatic breast cancer.
Buendia-Buendia J, Cohen O, Kim D, Jain E, Winer E, Lin N, Wagle N. Characterization of mutational processes in ER+ metastatic breast cancer. Journal Of Clinical Oncology 2019, 37: 1019-1019. DOI: 10.1200/jco.2019.37.15_suppl.1019.Peer-Reviewed Original ResearchMetastatic breast cancerEarly-stage breast cancerSubset of patientsStage breast cancerWhole-exome sequencingBreast cancerManagement of MBCMutational signaturesMBC samplesMetastatic tumor biopsiesNormal aging processEndocrine therapyMetastatic settingCancer Genome AtlasClinical featuresClinical trialsDisease progressionTumor biopsiesPrimary biopsiesMutational burdenTumor evolutionBreast tumorsMBC tumorsCancerTumor samples
2016
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Stover DG, Coloff JL, Barry WT, Brugge JS, Winer EP, Selfors LM. The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis. Clinical Cancer Research 2016, 22: 6039-6050. PMID: 27330058, PMCID: PMC5161615, DOI: 10.1158/1078-0432.ccr-16-0471.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNeoadjuvant chemotherapyPathologic complete responseBreast cancerGene expression signaturesComplete responseExpression signaturesPrimary breast cancer biopsiesImmune activation signatureBreast cancer biopsiesRole of proliferationClinicopathologic characteristicsSignature scoreImmune activityCancer biopsiesPAM50 subtypesBreast tumorsProliferation differencesCancerActivation signatureNeoadjuvant chemosensitivityChemosensitivityTumorsDNA damageScores
2015
PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers
Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene 2015, 35: 3607-3612. PMID: 26500061, PMCID: PMC4846581, DOI: 10.1038/onc.2015.406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHumansLapatinibMammary Neoplasms, ExperimentalMice, KnockoutMolecular Targeted TherapyPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2Signal TransductionThiazolesTumor BurdenXenograft Model Antitumor AssaysConceptsBreast tumorsP110β inhibitorsHuman epidermal growth factor receptor 2 (HER2) amplificationP110α inhibitionPTEN lossInhibition of HER2Treatment of HER2Human cancersPI3K pathway activationPTEN-deficient breast cancersGenetic mouse modelsPI3K/Akt signalingPTEN-deficient tumorsPI3K/AktDual HER2Therapeutic regimenHER2 inhibitionPIK3CA mutationsTumor regressionBreast cancerMouse modelXenograft modelHER2Null tumorsHER2 activation
2011
P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer.
Sprecher E, Lezon-Geyda K, Sarkar S, Bossuyt V, Narayaan M, Kumar A, Krop I, Winer E, Tuck D, Kleinstein S, Harris L. P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer. Cancer Research 2011, 71: p1-06-23-p1-06-23. DOI: 10.1158/0008-5472.sabcs11-p1-06-23.Peer-Reviewed Original ResearchPathologic complete responseBreast cancer patientsBreast cancer cell linesSensitive cell linesCancer cell linesCancer patientsSingle doseBreast cancerHER2-positive early-stage breast cancerPositive early-stage breast cancerCell linesBreast tumorsEarly breast cancer patientsEarly-stage breast cancerDose of trastuzumabEarly-stage HER2Early breast cancerResistant breast tumorsStage breast cancerTumor core biopsiesPathway analysisMechanism of actionResistant HER2RECIST criteriaClinical responseAdjuvant chemotherapy in luminal breast cancers
Lim E, Winer EP. Adjuvant chemotherapy in luminal breast cancers. The Breast 2011, 20: s128-s131. PMID: 22015279, DOI: 10.1016/s0960-9776(11)70309-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Agents, HormonalBiomarkersBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm StagingNeoplasms, Hormone-DependentPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsAdjuvant endocrine therapyLuminal breast cancerEndocrine therapyBreast cancerEstrogen receptorAdjuvant chemotherapyProgesterone receptorHER2-negative breast cancerER-positive breast tumorsAddition of chemotherapyER-positive diseaseER-positive tumorsUse of chemotherapySubset of patientsSubgroup of patientsER-negative tumorsAdditional therapyCytotoxic chemotherapyEndocrine sensitivityClinicians' estimationTherapeutic responseFavorable outcomeCurrent biomarkersChemotherapyBreast tumorsAssociation between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors
Sprecher E, Sarkar S, Kleinstein S, Narayan M, Winer E, Tuck D, Lezon-Geyda K, Krop I, Harris L. Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors. 2011, 446-450. DOI: 10.1145/2147805.2147867.Peer-Reviewed Original ResearchEarly-stage HER2Breast cancer patientsBreast tumorsTrastuzumab treatmentCancer patientsCell linesHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer settingGrowth factor receptor 2Resistant breast tumorsTrastuzumab-resistant HER2Breast cancer cell linesClinical treatment decisionsFactor receptor 2Trastuzumab exposureCancer cell linesGene expression signaturesResponsive patientsTrastuzumab resistanceSingle doseTargeted therapyBreast cancerCancer settingTreatment decisions